Celiac Disease and Gluten Sensitivity Have More Intraepithelial Lymphocytes

Dr. Scot Lewey

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Intraepithelial lymphocytes (IEL’s) are specialized white blood cells present in increased in number in the villous tips of the small intestine. They are believed critical in the development of celiac disease (CD). Though not specific for CD, increased IEL’s are accepted as the earliest sign of gluten intolerance in the gut. Most pathologists either report the number of IEL’s per 20 intestinal lining cells (enterocytes) or per 100 enterocytes. Celiac disease is an autoimmune disease of gluten intolerance or sensitivity not a food allergy though many people mistakenly refer to it as gluten allergy or wheat allergy. Previously thought to be rare it is now known to be very common, affecting 1/100 worldwide.

Celiac Sprue, as CD is also commonly known, is definitively diagnosed by the combination positive results for specific blood antibodies for CD, either endomysial (EMA) or tissue transglutaminase (tTG); a characteristic small intestine biopsy; and response to a gluten-free diet (GFD). Classically, flattening of the intestinal villi, known as villous atrophy, has been the gold standard for diagnosis. Positive EMA or tTG tests without vilous atrophy on biopsy but increased IEL's is accepted as diagnostic in the context of response to GFD, especially when an individual is positive for one of the two predisposing genes, DQ2 or DQ8.

For more than 30 years >40 IEL’s/100 enterocytes was considered the diagnostic threshold for CD. That number has been reduced to >30/100. More recent studies have indicated it may need to be lowered to >20-25/100. The significance of lower numbers of IEL's is debated.

Helicobacter pylori bacteria infection, giardia parasite infection, cow’s milk protein sensitivity, and viral infections have all been reported associated with increased duodenal IEL’s. Though not well established, it is believed that the number of IEL’s in these conditions may not be as high as in CD.

Inflammatory conditions in the esophagus, stomach, distal small bowel or colon may be associated with increased IEL’s in those areas but the number has not been well studied. There is a concern that some pathologists may falsely attribute increased duodenal IEL’s to associated inflammation going on in either the esophagus or stomach. Increased IEL’s have been noted in the gut above the duodenum (esophagus and stomach) and below the jejunum (ileum and colon) in both celiac and microscopic or collagenous colitis caused by gluten sensitivity.

A recent study of biopsies of the esophagus, stomach, and duodenum of 46 people without evidence of CD reached several conclusions. Though there may be a slight increase IEL’s in esophagitis and gastritis, the difference in IEL numbers is not significantly different in normal biopsies of the esophagus and stomach. Though general ranges of duodenal IEL's found in active esophagitis (2-13, average 8.8), active gastritis with Helicobacter pylori infection (2-13, average 7.2) and chronic gastritis without H. pylori infection (4-20, average 10.2) was very similar to those with negative esophagus, stomach and duodenal biopsies (2-18, average 6.7) the average number of IEL's was slightly higher, though not statistically significant.

More importantly, in my opinion, I believe this study showed that the numbers of IEL’s in people with normal biopsies, esophagitis and gastritis were significantly lower than those reported in CD (>30/100 ) and early gluten injury (20-25 IEL’s/100 enterocytes) not meeting diagnostic criteria for CD. I believe this study is helpful because it argues against attributing more than 20-25 IEL’s/ 100 enterocytes to other inflammatory processes in the esophagus or stomach. It also supports the findings of other studies that have found that >20-25 IEL’s/100 are early signs of gluten sensitivity.

In the context of elevated gliadin antibody levels I believe that >25 IEL’s more likely than not indicates gluten sensitivity though not necessarily CD. Strict criteria for diagnosing CD require a positive specific CD blood test such as endomysial antibody or tissue transglutaminase antibody and >30 IEL’s/100 enterocytes and/or evidence of villous atrophy on small intestinal biopsy.

For more information about IEL’s, including illustrative biopsy photos, see my website www.thefooddoc.com

Copyright 2006 The Food Doc, LLC, All Rights Reserved.


Yousef MM, Yantiss RK, Baker SP and Banner BF. Duodenal Intraepithelial Lymphocytes in Inflammatory Disorders of the Esophagus and Stomach. Clinical Gastroenterology and Hepatology 2006;4:631-634.

Dr. Scot Lewey, a food allergy expert-the food doc, is a medical doctor specializing in diseases of the digestive tract (gastroenterologist). For over two decades he has been practicing medicine, writing articles, and participating in research. A practicing physician who diagnoses and treats Celiac disease, food intolerance, food allergies, colitis, Crohn's disease, irritable bowel syndrome, stomach ulcers and acid reflux he is also personally is gluten and casein sensitive. He shares his unique and timely insights on his website at http://www.thefooddoc.com that is dedicated to helping people choose the “right foods to feel right".


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